Injury to the spinal cord initiates a complex cascade of events, the net effect of which is a behaviorally limiting neurological deficit. Innumerable investigations of spinal cord injury have led to the realization that in order to improve the neurological outcome of patients we must first understand the basic mechanisms that promote differentiation and growth in the developing nervous system and regeneration and repair in the adult. This program project is designed as a coordinated effort to identify basic cellular mechanisms influencing degeneration and regeneration in the CNS following injury. The ultimate goal of the proposed studies is to develop a body of knowledge sufficient for identifying and understanding basic mechanisms which may be susceptible to intervention strategies leading to an improvement in neurological outcome. The program is divided into 6 major areas: 1) A core facility providing for electronmicroscopy studies; 2) A core facility providing for administrative support; 3) Studies focussed on trophic factors and membrane components that may influence regeneration; 4) Analyses of mechanisms influencing sprouting and reactive synaptogenesis; 5) Characterization of functional capacities of regenerating neurons including the activity of voltage-dependent channels; and 6) Cytochemical and genetic mechanisms underlying regeneration and the role of the genome in reactivating specific developmental genes potentially important in regenerative responses. These studies will fill critical gaps in our current understanding of regenerative responses in the developing and adult CNS. This knowledge is not only crucial for the development of successful strategies for treating spinal cord injury but also for injuries elsewhere in the CNS as well as disease processes involving the progressive loss of populations of neurons such as occurs in Alzheimer's dementia.